The UC San Diego AntiViral Research Center sponsors weekly presentations by infectious disease clinicians, physicians and researchers. The goal of these presentations is to provide the most current research, clinical practices and trends in HIV, HBV, HCV, TB and other infectious diseases of global significance. The slides from the AIDS Clinical Rounds presentation that you are about to view are intended for the educational purposes of our audience. They may not be used for other purposes without the presenter’s express permission.

AIDS CLINICAL ROUNDS

!!ADDIS&VP:!

Screening!of!TB,!HIV!and!Syphilis!!in!an!Ethiopian!Prison!in!Addis!Ababa!!

!Jill!Blumenthal,!MD!

AIDS!Rounds!October!2,!2015!

Disclosures*

•  I*have*no*relevant*disclosures*

Introduc2on*

•  Ac2ve*Disease*Screening*to*Decrease*TB,*HIV,*and*Syphilis*in*a*Vulnerable*Popula2on*(ADDIS@VP)*is*an*implementa2on*research*study*of*screening*for*TB,*HIV,*and*syphilis*in*a*large*Ethiopian*Prison.**

Research*Team*EPHA!•  Wondwossen*Amogne*(MD,*MSc),*Principal*Inves2gator*•  Eliyas*Tsegaye*(MD,*MPHM),*Co@PI*•  Tsegahun*Manyazewal*(PhD,*MSc),*Research*Coordinator*•  Habtamu*Woldeamanuel*(BSc)*Data*Manager*FPA!!•  Lemma*Teferra*(MD,*MPH),*Co@PI!UCSD!•  *Allen*McCutchan*(MD,*MSc),*Vice*PI*•  *Jill*Blumenthal*(MD),*Co@Inves2gator*•  *Jason*Young*(PhD),*Biomedical*Informa2cs*Coordinator*•  *Mike*Duszynski*(MHA,*FACHE),*Program*Manager*CDC!•  Melissa*Briggs*(MD,*MPH),*CDC*Project*Technical*Officer**

Implemen2ng*partners*/*ADDIS@VP*Project**

•  Ethiopian Public Health Association (EPHA)

•  Ethiopian Federal Prison Administration

(FPA)

•  University of California, San Diego (UCSD) •  US Centers for Disease Control &

Prevention (CDC) / CDC-Ethiopia

6

Epidemiology!of!!HIV!in!Ethiopia!

•  Population: 90 million •  HIV Prevalence: 1.3% (F:1.8%, M:0.9%)

•  Urban: 2.6%, Rural: 0.5% •  Annual HIV Incidence: 0.03% = 20,000 •  Adult PLHIV: 759,000

•  Male: 39% / Female: 61% •  Patients on ART

•  Ever started on ART = 379,190 •  Currently eligible for ART = 398,686 •  Currently on ART = 274,708 (71.5%)

*

Epidemiology of TB

in Ethiopia and its prisons

–  Prevalence*es2mates*have*been*revised*downward*by*2/3,*but*methodology*is*variable*and*not*based*on*current*laboratory*methods*

•  2011*=*237*cases/100,000*•  2013*=*80*cases/100,000*

–  Incidence*=*258*case/100,000*–  TB/HIV*co@infec2on*rate*was*8%*–  Prevalence*of*MDR@TB**

•  1.6%*for*all*new*TB*cases*•  11.8%*for*retreatment*cases*

TB*in*Prisons*– TB*incidence*rates*in*prisons*are*o_en*5*to*10*2mes*higher*than*na2onal*rates*in*general*popula2ons.**

– Prison@specific*risk*factors*for*TB:*•  *increased*exposure*to*aerosols*of*MTb*from*crowding*and*poor*ven2la2on*

•  *poor*nutri2on**•  *heat*/*cold*stress.***

TB*prevalence*in*Ethiopian*Prisons A*survey*of*2,300*prisoners*in*2008*in*3*prisons:**

•  16%*had*cough*of*≥*2*wks*•  9%*were*smear@*or*culture@posi2ve**•  Prevalence*of*PTB*was*1,913/100,000*(~2%),*seven!Qmes!higher*than*the*general*Ethiopian*popula2on.**

•  Factors*associated*with*PTB:*•  younger*age*(OR=3.7)*•  urban*residence*(OR=3.6)**•  cough*>4*weeks*(OR=3.2)**•  sharing*a*cell*with*a*TB*pa2ent*(OR=3.*4).**

–  Knowledge*about*TB*low*

Epidemiology of Syphilis

in Ethiopia *

*•  Syphilis:!•  Prevalence*of*syphilis*based*on*RPR*ranges*from*<1@3%*in*urban*antenatal*clinics*,*blood*donors**and*factory*workers.*

•  No*es2mates*for*Ethiopia*prisoner*popula2ons*are*available.*

•  Prevalence*in*Ghanaian*prisoners*16.5%.***•  Thus,*we*an2cipated*a*prevalence*of**~15%*in*residents*of*Kality*Prison.**

Kality*Prison*•  Largest*of*5*federal*prisons*and*only*one*with*more*than*

rudimentary*medical*facili2es.*

•  Located*15*km*from*Addis*Ababa**

•  Serves*both*for*long@term*deten2on*holding*for*federal*courts**and*transit*between*other*federal*prisons.***

–  Resident*prisoner*census*is*about*3,500.**•  Components*

– Main*prison*(high*security*area)*is*divided*into*8*zones.**

–  Lower*security*area*contains*HIV,*TB,*and*other*clinics*and*a*40@bed*ward.*

–  Federal*Prison*Administra2on*General*Hospital,*a*120@bed*facility*the*with*a*clinical*laboratory,*and*XR*department*equipped*with*digital*imager*by*the*ADDIS@VP*study**

Kality*Prisoners*

– Prisoners*tend*to*be*young,*male,*poor,*substance@addicted*(especially*to*tobacco*and*alcohol,*but*not*other*drugs)*and*poorly*nourished,*but*unknown*propor2on*of*poli2cal*prisoners*may*differ.****

– Risk*factors*for*clinical*TB,*HIV,*and*syphilis*may*be*increased*before*entering*the*prison,*and*the*prison*environment*further*predisposes*to*reac2va2on*and*transmission*of*TB*

TB*in*Kality*Prison*

•  Pilot*survey*prior*to*ADDIS@VP*study*from*April*@*June*/2011*found*higher*prevalence*of*TB*symptoms*and*HIV*an2body*in*residents*than*entrants*sugges2ng*transmission*of*both*diseases*within*the*prison.*

– Prevalence*of*symptoms*sugges2ve*of*TB*16*fold*higher*(22.3/1.4%)**

– Prevalence*of*HIV*was*4*2mes*higher*(15.2/3.6%)*

Pilot*Study*at*Kality*Prevalence!of!TB!and!HIV!in!Prison*

Prevalence!of!at!least!1!symptom!of!!pulmonary!TB!

Prevalence!of!HIV!anQbody!**

Entrants* 22/1,582***(1.4%)!

10/279***(3.6%)*

Residents* 594/2,666***(22.3%)*

42/277***(15.2%)!

!Limita2ons*of*Pilot*Study*

*TB!!•  Es2mates*of*poten2al*TB*cases*were*based*on*self@reported*symptoms*without*clinical,*lab,*or*CXR*evalua2ons!

HIV!•  Es2mates*were*based*on*voluntary*par2cipa2on*in*screening*and*thus*subject*to*substan2al*biases**

•  Behaviors*that*may*contribute*to*this*transmission*include*pros2tu2on,*sex*between*men,*and*sharing*of*blood*contaminated*sharp*materials*for*shaving*,*taoooing*and*other*purposes.*

Kality*Prison*medical*staff*– 3*full@2me*physicians*–  *9*health*officers*(physician’s*assistants)*–  *41*clinical*nurses*–  *3*radiography*technicians*–  *6*laboratory*technicians*–  *1*part@2me*physician/radiologist**

Availability*of*Treatment**for*Targeted*Diseases*at*Kality*

•  Provided by current prison staff according to Ethiopian guidelines and not mandated or provided by the study ! Tuberculosis

•  Admitted to prison hospital for consolidated therapy

•  Four-drug directly observed therapy (DOT) ! MDR-TB

•  Referral to St. Peters Specialist Hospital or Defense MDR-TB facility

! HIV •  ART provided on-site

! Syphilis •  Penicillin regimens available on-site

Scien2fic*Jus2fica2on*for*ADDIS@VP*Study*

– First*laboratory@based*prevalence*survey*of*TB,*HIV*and*STI*(syphilis)*in*an*Ethiopian*prison*supported*by*culture*and*nucleic*acid*based*diagnos2c*technologies**

– Builds*on*improved*diagnos2c*and*treatment*capacity*for*HIV,*TB*,and**STIs*provided*PEPFAR@sponsored,*UCSD@implemented,*assistance*program***

– Will*examine*jus2fica2on*(costs/benefits)*and*capacity*of*implementa2on*of*screening*of*TB,*HIV*and*other*STIs*in*Ethiopian*prisons**

Ethical*Jus2fica2on*•  The*study*meets*criteria*qualifying*research*studies*for*

involvement*of*prisoners*by:*

–  Addressing*issues*relevant*to*prisoners:*transmission*of*serious*and*treatable*diseases*(TB,*HIV,*and*syphilis)*in*prisoners*

–  Benefirng*prisoners:*enabling*diagnosis,*treatment,*and*suppression*of*transmission*of*3*life@threatening*diseases*(in*spite*of*their*detec2on*predisposing**to*s2gma*and*discrimina2on)*

–  Posing*only*minimal*risks*because:**

•  Screening*procedures*are*minimally*invasive*(sputum*collec2on,*drawing*blood*and*CXRs).**

•  Treatments*are*substan2ally*beneficial*and*well*tolerated*

Ethical*Jus2fica2on*(cont)*–  Involving*no*unapproved*diagnos2c*methods,*drugs*or*treatment*strategies**

– Assuring*that*par2cipa2on*is*voluntary*through*educa2on*and*wrioen*informed*consent**

– Passing*review*by*3*IRBs*that*have*US*DHH*Federal@Wide*Assurance*(FWA)*accredita2on*and*are*competent*and*empowered*to*review*research*involving*prisoners:**

•  Na2onal*Ministry*of*Science*and*Technology*(MoST)*•  EPHA*•  UCSD*

Objec2ves*

•  Primary!ObjecQve!– To*compare*prevalence*of*TB,*HIV*and*syphilis*in*the*in*entrant*versus*resident*inmates*to*detect*evidence*of*intramural*transmission*in*the**prison.***

Secondary*Objec2ves*•  To*es2mate*incidence*rates*of*TB,*HIV*and*syphilis*in*the*

popula2on*over*the*course*of*the*study*

•  To*evaluate*the*added*u2lity*compared*to*sputum*microscopy,*GeneXpert,*Liquid*sputum*culture*and*CXR*for*detec2on*of*TB*cases*

•  To*evaluate*the*correlates*of*radiographic*evidence*of*TB*by:*–  describing*the*propor2on*of*pa2ents*pulmonary*TB*by*chest*imaging*who*are*diagnosed*with*TB*based*on*either*a)*sputum*microscopy,*or*b)*Xpert*or*c)*sputum*culture*

–  comparing*types*of*radiographic*evidence*of*TB*by*HIV*status,*CD4*count*categories*and*ART*status**

Secondary*objec2ves*(cont)*•  To*describe*prevalence*of*drug*resistant*M.*Tb*by*two*

methods:*GenXpert*(genotypic)*assay*and*liquid*culture*assays*

•  To*detect*evidence*of*clustering*of*TB*cases*by*zone*within*the*prison*

•  To*compare*the*clinical*presenta2ons*and*treatment*outcomes*of*persons*diagnosed*by*ac2ve*screening*to*those*detected*by*the*currently@prac2ced,*passive*(self@referral)*methods*of*detec2ng*TB.**

•  To*describe*the*administra2ve*and*logis2cal*barriers*and*costs*of*the*screening*program*

•  To*describe*barriers*to*par2cipa2on*by*prisoners*in*the*screening*program*

Major*Hypotheses*•  Primary!Hypothesis:**

– Prevalence*rates*of*ac2ve*pulmonary*TB,*HIV*and*syphilis*in*resident*will*exceed*those*in*entrants.***

•  Secondary!Hypotheses:*–  Incidence*of*TB,*HIV*and*syphilis*will*decrease*between*the*two*prevalence*surveys*in*residents*one*year*apart**

– Addi2on*to*sputum*microscopy*of:*a)*GeneXpert*tes2ng*for*TB,*b)*CXRs,*and*c)*sputum*culture*will*increase*detec2on*of*pulmonary*TB*

Selec2on*and*Enrollment*of*Subjects*•  Inclusion Criteria

– Current prisoner of Kality Prison, either

newly entering the prison or a resident of the

prison.

– Men or women age 18 years or older

– Ability and willingness to provide written

informed consent

Selec2on*and*Enrollment*of*Subjects*•  Exclusion Criteria

– Any condition that causes cognitive

impairment such as severe acute illness or

injury, developmental retardation, or severe

psychiatric illness and thus precludes

informed consent or safely participating in

its procedures

– For residents, screening at entry within the

past 30 days

Study*Schedule*

– Overall: 09/2014 until 03/2016 – Entrants: 18 months of the study – Residents: 2 rounds

• 1st round: 11/14 to 3/15 (completed) • 2nd round: 11/15 to 3/16

Laboratory*Tes2ng*•  3*labs*involved:*FPA,*ICL*and*AARL** Sample! FPA! ICL! AARL/FPA!

Sputum!for*TB* AFB*(3x)* AFB* *****GeneXpert*

GeneXpert** Culture*

@@@@* DST* @@@@*

Blood/Serum*for*HIV*&*Syphilis*

HIV*Rapid*Test*

ELISA*test*for*HIV*

@@@@**

RPR*Strip*Test*for*Syphilis*

RPR*Titra2on*Test*for*Syphilis*

@@@@*

Data*Management*•  SOPs*and*CRFs*were*developed*for*each*aspect*of*

data*collec2on*•  The*ADDIS@VP*data*group*located*at*the*Prison*

Hospital*collects*CRFs*from*the*prison*staff*and*labs*and*enters*them*into*OCCAMS*via*internet*to*a*UCSD*server**

•  The*UCSD@developed*OCCAMS*system*(Open@source,*Clinical*Content*Management*System)*employs*data*quality*monitoring*tools*to*support*data*integrity**

•  ADDIS@VP*sta2s2cal*groups*provides*biweekly*updates*of*study*progress**

Preliminary*Results*

•  N=6343*par2pants*(Entrants=*3314;*Residents=*3029)*– 86%*male*

– median*age*26*– 39%*Amharic*ethnicity*– 86%*literate*– 73%*Orthodox*Chris2an*– 92%*urban*residence*prior*to*prison*

HIV*Results*

•  Reported*HIV*prevalence*in*all*prisoners*=*1.8%*(80/4335)**–  E=17;*R=63*

•  Prevalence*of*new*diagnoses*–  E=*2.1%*(35/1659)**–  R=*2.5%*(65/2676)**

•  Prevalence*of*HIV*diagnoses*in*HIV+*prisoners*that*are*new*–  E=*63%*(22/35)*–  R=*54%*(35/65)**

**All*posi2ve*tests*confirmed*at*ICL**

*

Syphilis*Results*

•  Overall,*2.6*%*(43/1651)*entrants*and*3.6%*(98/2731)*with*posi2ve*RPR*results*

**All*posi2ve*tests*confirmed*at*ICL*

TB*Results*

•  N=15*report*current*an2@TB*therapy*•  N=12*report*an2@TB*therapy*within*1*year*•  4%*(203/5009)*report*an2@TB*therapy*ever*•  Par2cipants*are*TB!screen!posiQve!if*they*endorse*any*of*6*TB*screening*ques2ons*(cough*x2*weeks,*fever,*hemoptysis,*night*sweats,*weight*loss*+*HIV*with*any*cough)*

TB*Results*(cont)*

•  TB*Screen*posi2ve*–  E=*8%*(155/1980)**–  R=*39%*(1167/3029)*–  Cough*most*o_en*reported*followed*by*fever*and*night*sweats*

•  Sputum*produc2on*in*those*who*are*TB*Screen*posi2ve*–  E=*38%*(59/155)**–  R=*69%*(805/1167)**

•  TB*posi2vity*–  4!samples!posi2ve*for*AFB*by*sputum*microscopy,*culture*and*Xpert*(Point*prevalence*of*0.08%)*

–  DST*found*2*samples*with*INH@resistance;*1*with*PZA@resistance*

CXR*Results*Technician

!

Radiologist!

Probable* Possible* Unlikely* Total*

Probable* 1! 6* 10* 17*

Possible* 7* 0* 1* 8*

Unlikely** 24* 27* 704! 755*

Total* 32* 33* 715* 780*

Administra2ve*and*Logis2cal*Barriers**Study@related*1.  Group*informed*consent*process*may*lead*to*contagion*of*nega2vity*and*

study*refusal*2.  Poor*communica2on*of*clinical*data*between*radiologist*and*technicians*

Inadequate*space*for*personnel*and*records*in*data*rooms**3.  Payment*to*prison*study*staff*per*data*form**4.  For*“security”*reasons*EPHA*and*UCSD*study*staff*have*no*access*to*the*

resident*areas*of*the*prison*5.  Incen2ves*to*par2cipants*logis2cally*difficult*Screening@related*1.  Screening*of*entrants*is*difficult*due*to*unpredictable*arrival*2mes*and*

high*in*numbers*arriving*together*2.  Understaffing*of*prison*guards*delays*comple2ng*study*procedures*and*

may*lead*to*withdrawal*of*coopera2on*by*consented*prisoners**

*

Study*Status*

•  Retraining*of*study*staff*in*October*•  Second*resident*sweep*to*begin*November*1*•  Refining*linkage*to*care*prac2ce*•  Chart*abstrac2on*to*begin*in*October**

References*•  Asmamaw*D,*Seyoum*B,*Makonnen*E,*Atsebeha*H,*Woldemeskel*D,*Yamuah*L,*Addus*H,*Aseffa*A.*Primary*drug*resistance*in*

newly*diagnosed*smear*posi2ve*tuberculosis*pa2ents*in*Addis*Ababa,*Ethiopia.*Ethiop.*Med.*J.*2008*46:367@74.*•  Abebe,*DS,*Bjune,*G,*Ameni,*G,*Biffa,*D,*Abebe,*F.*Prevalence*of*pulmonary*tuberculosis*and*associated*risk*factors*in*

Eastern*Ethiopian*prisons.**Int*J*Tuberc*Lung*Dis.*2011;115:668@73.**•  Braun*MM,*Truman*BJ,*Maguire*B,*et*al.*Increasing*incidence*of*tuberculosis*in*a*prison*inmate*popula2on.*Associa2on*with*

HIV*infec2on.*JAMA*1989;*261:*393@397.*

•  Coninx*R,*Mathieu*C,*Debacker*M,*et*al.*First@line*tuberculosis*therapy*and*drug@resistant*Mycobacterium*tuberculosis*in*prisons.*Lancet*1999;*353:*969@973.*

•  Coninx*R,*Maher*D,*Reyes*H,*Grzemska*M.*Tuberculosis*in*prisons*in*countries*with*high*prevalence.*BMJ*2000;*320:*440@442.*

•  Corbeo,*E*Bandason,*E*Duong,*Ethel*T**Beauty*D,**et*al*Comparison*of*two*ac2ve*case@finding*strategies*for*community@based*diagnosis*of*symptoma2c*smear@posi2ve*tuberculosis*and*control*of*infec2ous*tuberculosis*in*Harare,*Zimbabwe*(DETECTB):*a*cluster@randomised*trial*Lancet.*2010;*376:*1244–12*

•  Kebede*Y.,*Pickering*J.,*McDonald*J.,*Zewde*D.*HIV*Infec2on*in*an*Ethiopian*Prison.*Am.*J.*Public*Health*1991;*81:625@627*•  Legrand,*J,*Sanchez,*A,*Le*Pont,*F,*Camacho*L,*Larouze,*B*Modeling*the*Impact*of*Tuberculosis*Control*Strategies*in*Highly*

Endemic*Overcrowded*Prisons*PLOS*2008*3:2100@2105*•  March*F,*Coll*P,*Guerrero*RA,*et*al.*Predictors*of*tuberculosis*transmission*in*prison:*an*analysis*using*conven2onal*and*

molecular*methods.*AIDS*2000;*14(5):*525@535.*

•  Mar2n*V,*Alvarez@Guisasola*F,*Cayla*JA,*Alvarez*JL.*Predic2ve*factors*of*Mycobacterium*tuberculosis*infec2on*and*pulmonary*tuberculosis*in*prisoners.Int*J*Epidemiol*1995;*24:*630@636.*

•  Reed*S,*Mamoc*G,*Gossad,*E,*Jasura,*M,*Getahune*M,*Lemmae,*E,*Mathews,*C,*and*McCutchan*JA.*Improved*tuberculosis*smear*detec2on*in*resource@limited*serngs:*Combined*bleach*concentra2on*and*LED*fluorescence*microscopy*Interna2onal*Health*2011**

•  Tessema,*B,*Yismaw*G,*KassuG*,Amsalu,*A,*,*Mulu*A*et*al*Seroprevalence*of*HIV,*HBV,*HCV*and*syphilis*infec2ons*among*blood*donors*at*Gondar*University*Teaching*Hospital,*Northwest*Ethiopia:*declining*trends*over*a*period*of*five*years*BMC*Infec2ous*Diseases*2010;*10:111@115*

Acknowledgements*

•  Special*thanks*to*Drs.*McCutchan*and*Eliyas*•  None*of*this*study*could*be*possible*without*the*hard*work*and*dedica2on*of*Mike*Duszynski*